tbuckley/cabot-search huggingface dataset:
Comprehensive assessment of differential ChIP-seq tools guides optimal algorithm selection
Authors: Thomas Eder, Florian Grebien
Journal: Genome biology (2022)

The analysis of chromatin binding patterns of proteins in different biological states is a main application of chromatin immunoprecipitation followed by sequencing (ChIP-seq). A large number of algorithms and computational tools for quantitative comparison of ChIP-seq datasets exist, but their performance is strongly dependent on the parameters of the biological system under investigation. Thus, a systematic assessment of available computational tools for differential ChIP-seq analysis is required to guide the optimal selection of analysis tools based on the present biological scenario.We created standardized reference datasets by in silico simulation and sub-sampling of genuine ChIP-seq data to represent different biological scenarios and binding profiles. Using these data, we evaluated the performance of 33 computational tools and approaches for differential ChIP-seq analysis. Tool performance was strongly dependent on peak size and shape as well as on the scenario of biological regulation.Our analysis provides unbiased guidelines for the optimized choice of software tools in differential ChIP-seq analysis.
Pre-exposure prophylaxis with 300 mg Evusheld elicits limited neutralizing activity against the Omicron variant
Authors: Ilies Benotmane, Aurélie Velay, Gabriela Gautier-Vargas, Jérôme Olagne, Olivier Thaunat, Samira Fafi-Kremer, Sophie Caillard
Journal: Kidney International (2022)
Realigning the LIGHT signaling network to control dysregulated inflammation
Authors: Carl F. Ware, Michael Croft, Garry A. Neil
Journal: The Journal of Experimental Medicine (2022)

Advances in understanding the physiologic functions of the tumor necrosis factor superfamily (TNFSF) of ligands, receptors, and signaling networks are providing deeper insight into pathogenesis of infectious and autoimmune diseases and cancer. LIGHT (TNFSF14) has emerged as an important modulator of critical innate and adaptive immune responses. LIGHT and its signaling receptors, herpesvirus entry mediator (TNFRSF14), and lymphotoxin β receptor, form an immune regulatory network with two co-receptors of herpesvirus entry mediator, checkpoint inhibitor B and T lymphocyte attenuator, and CD160. Deciphering the fundamental features of this network reveals new understanding to guide therapeutic development. Accumulating evidence from infectious diseases points to the dysregulation of the LIGHT network as a disease-driving mechanism in autoimmune and inflammatory reactions in barrier organs, including coronavirus disease 2019 pneumonia and inflammatory bowel diseases. Recent clinical results warrant further investigation of the LIGHT regulatory network and application of target-modifying therapeutics for disease intervention.
Screen Timing May Be More Likely Than Screen Time to Be Associated With the Risk of Autism Spectrum Disorder—Reply
Authors: Megumi Kushima, Zentaro Yamagata
Journal: JAMA Pediatrics (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
NOTCH1 signaling during CD4+ T-cell activation alters transcription factor networks and enhances antigen responsiveness
Authors: Alec B. Wilkens, Elena C. Fulton, Margot J. Pont, Gabriel O. Cole, Isabel Leung, Sylvia M. Stull, Matthew R. Hart, Irwin D. Bernstein, Scott N. Furlan, Stanley R. Riddell
Journal: Blood (2022)
Coexistence of pachyonychia congenita and hidradenitis suppurativa: more than a coincidence
Authors: Mor Pavlovsky, Alon Peled, Ofer Sarig, Nadav Astman, Liron Malki, Odile Meijers, Sari Assaf, Janice Schwartz, Kiril Malovitski, David Hansen, Eli Sprecher, Liat Samuelov
Journal: British Journal of Dermatology (2022)

The coexistence of pachyonychia congenita (PC) and hidradenitis suppurativa (HS) has been described in case reports. However, the pathomechanism underlying this association and its true prevalence are unknown.To determine the genetic defect underlying the coexistence of PC and HS in a large kindred, to delineate a pathophysiological signalling defect jointly leading to both phenotypes, and to estimate the prevalence of HS in PC.We used direct sequencing and a NOTCH luciferase reporter assay to characterize the pathophysiological basis of the familial coexistence of HS and PC. A questionnaire was distributed to patients with PC registered with the International Pachyonychia Congenita Research Registry (IPCRR) to assess the prevalence of HS among patients with PC.Direct sequencing of DNA samples obtained from family members displaying both PC and HS demonstrated a missense variant (c.275A>G) in KRT17, encoding keratin 17. Abnormal NOTCH signalling has been suggested to contribute to HS pathogenesis. Accordingly, the KRT17 c.275A>G variant resulted in a significant decrease in NOTCH activity. To ascertain the clinical importance of the association of HS with PC, we distributed a questionnaire to all patients with PC registered with the IPCRR. Seventy-two of 278 responders reported HS-associated clinical features (25·9%). Disease-causing mutations in KRT17 were most prevalent among patients with a dual phenotype of PC and HS (43%).The coexistence of HS and KRT17-associated PC is more common than previously thought. Impaired NOTCH signalling as a result of KRT17 mutations may predispose patients with PC to HS. What is already known about this topic? The coexistence of pachyonychia congenita (PC) and hidradenitis suppurativa (HS) has been described in case reports. However, the pathomechanism underlying this association and its true prevalence are unknown. What does this study add? A dual phenotype consisting of PC and HS was found to be associated with a pathogenic variant in KRT17. This variant was found to affect NOTCH signalling, which has been previously implicated in HS pathogenesis. HS was found to be associated with PC in a large cohort of patients with PC, especially in patients carrying KRT17 variants, suggesting that KRT17 variants causing PC may also predispose to HS. What is the translational message? These findings suggest that patients with PC have a higher prevalence of HS than previously thought, and hence physicians should have a higher level of suspicion of HS diagnosis in patients with PC.
Medicare Advantage Enrollment Growth
Authors: Gretchen A. Jacobson, David Blumenthal
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Results of untargeted analysis using the SOMAscan proteomics platform indicates novel associations of circulating proteins with risk of progression to kidney failure in diabetes
Authors: Hiroki Kobayashi, Helen C. Looker, Eiichiro Satake, Pierre Jean Saulnier, Zaipul I. Md Dom, Kristina O’Neil, Katsuhito Ihara, Bozena Krolewski, Andrzej T. Galecki, Monika A. Niewczas, Jonathan M. Wilson, Alessandro Doria, Kevin L. Duffin, Robert G. Nelson, Andrzej S. Krolewski
Journal: Kidney International (2022)

This study applies a large proteomics panel to search for new circulating biomarkers associated with progression to kidney failure in individuals with diabetic kidney disease. Four independent cohorts encompassing 754 individuals with type 1 and type 2 diabetes and early and late diabetic kidney disease were followed to ascertain progression to kidney failure. During ten years of follow-up, 227 of 754 individuals progressed to kidney failure. Using the SOMAscan proteomics platform, we measured baseline concentration of 1129 circulating proteins. In our previous publications, we analyzed 334 of these proteins that were members of specific candidate pathways involved in diabetic kidney disease and found 35 proteins strongly associated with risk of progression to kidney failure. Here, we examined the remaining 795 proteins using an untargeted approach. Of these remaining proteins, 11 were significantly associated with progression to kidney failure. Biological processes previously reported for these proteins were related to neuron development (DLL1, MATN2, NRX1B, KLK8, RTN4R and ROR1) and were implicated in the development of kidney fibrosis (LAYN, DLL1, MAPK11, MATN2, endostatin, and ROR1) in cellular and animal studies. Specific mechanisms that underlie involvement of these proteins in progression of diabetic kidney disease must be further investigated to assess their value as targets for kidney-protective therapies. Using multivariable LASSO regression analysis, five proteins (LAYN, ESAM, DLL1, MAPK11 and endostatin) were found independently associated with risk of progression to kidney failure. Thus, our study identified proteins that may be considered as new candidate prognostic biomarkers to predict risk of progression to kidney failure in diabetic kidney disease. Furthermore, three of these proteins (DLL1, ESAM, and MAPK11) were selected as candidate biomarkers when all SOMAscan results were evaluated.
Prognostic impact of the updated 2018 <scp>HFA‐ESC</scp> definition of advanced heart failure: results from the <scp>HELP‐HF</scp> registry
Authors: Matteo Pagnesi, Carlo Mario Lombardi, Mauro Chiarito, Davide Stolfo, Luca Baldetti, Ferdinando Loiacono, Chiara Tedino, Luca Arrigoni, Daniele Ghiraldin, Daniela Tomasoni, Riccardo Maria Inciardi, Marta Maccallini, Alessandro Villaschi, Gaia Gasparini, Marco Montella, Stefano Contessi, Daniele Cocianni, Maria Perotto, Giuseppe Barone, Marco Merlo, Alberto Maria Cappelletti, Gianfranco Sinagra, Daniela Pini, Marco Metra
Journal: European Journal of Heart Failure (2022)

The Heart Failure Association of the European Society of Cardiology (HFA-ESC) proposed a definition of advanced heart failure (HF) that has not been validated, yet. We assessed its prognostic impact in a consecutive series of patients with high-risk HF.The HELP-HF registry enrolled consecutive patients with HF and at least one high-risk 'I NEED HELP' marker, evaluated at four Italian centres between 1st January 2020 and 30th November 2021. Patients meeting the HFA-ESC advanced HF definition were compared to patients not meeting this definition. The primary endpoint was the composite of all-cause mortality or first HF hospitalization. Out of 4753 patients with HF screened, 1149 (24.3%) patients with at least one high-risk 'I NEED HELP' marker were included (mean age 75.1 ± 11.5 years, 67.3% male, median left ventricular ejection fraction [LVEF] 35% [interquartile range 25%-50%]). Among them, 193 (16.8%) patients met the HFA-ESC advanced HF definition. As compared to others, these patients were younger, had lower LVEF, higher natriuretic peptides and a worse clinical profile. The 1-year rate of the primary endpoint was 69.3% in patients with advanced HF according to the HFA-ESC definition versus 41.8% in the others (hazard ratio [HR] 2.23, 95% confidence interval [CI] 1.82-2.74, p < 0.001). The prognostic impact of the HFA-ESC advanced HF definition was confirmed after multivariable adjustment for relevant covariates (adjusted HR 1.98, 95% CI 1.57-2.50, p < 0.001).The HFA-ESC advanced HF definition had a strong prognostic impact in a contemporary, real-world, multicentre high-risk cohort of patients with HF.
A New Agenda for Optimizing Investments in Community Mental Health and Reducing Disparities
Authors: Margarita Alegría, Jenny Zhen-Duan, Isabel Shaheen O’Malley, Karissa DiMarzio
Journal: American Journal of Psychiatry (2022)

The Biden-Harris Administration's FY22 budget includes $1.6 billion for the Community Mental Health Services Block Grant program, more than double the FY21 allocation, given the rising mental health crises observed across the nation. This is timely since there have been two interrelated paradigm shifts: one giving attention to the role of the environmental context as central in mental health outcomes, the other moving upstream to earlier mental health interventions at the community level rather than only at the individual level. An opportunity to reimagine and redesign the agenda of mental health research and service delivery with marginalized communities opens the door to more community-based care interventions. This involves establishing multisector partnerships to address the social and psychological needs that can be addressed at the community level rather than the clinical level. This will require a shift in training, delivery systems, and reimbursement models. The authors describe the scientific evidence justifying these programs and elaborate on opportunities to target investments in community mental health that can reduce disparities and improve well-being for all. They select levers where there is some evidence that such approaches matter substantially, are modifiable, and advance the science and public policy practice. They conclude with specific recommendations and the logistical steps needed to support this transformational shift.
Retraction Notice to: miR-135b Delivered by Gastric Tumor Exosomes Inhibits FOXO1 Expression in Endothelial Cells and Promotes Angiogenesis
Authors: Ming Bai, Jialu Li, Haiou Yang, Haiyang Zhang, Zhengyang Zhou, Ting Deng, Kegan Zhu, Tao Ning, Qian Fan, Guoguang Ying, Yi Ba
Journal: Molecular Therapy (2022)

Main text(Molecular Therapy 27, 1772–1783, October 2019)Molecular Therapy is retracting this article. After investigating concerns of image duplication raised by a reader, evidence for image duplication in identical or altered fashion in Figure 7B was identified. This reuse (and in part, misrepresentation) of data without appropriate attribution represents a severe abuse of the scientific publishing system. The authors do not agree to the retraction. Main text(Molecular Therapy 27, 1772–1783, October 2019)Molecular Therapy is retracting this article. After investigating concerns of image duplication raised by a reader, evidence for image duplication in identical or altered fashion in Figure 7B was identified. This reuse (and in part, misrepresentation) of data without appropriate attribution represents a severe abuse of the scientific publishing system. The authors do not agree to the retraction. (Molecular Therapy 27, 1772–1783, October 2019) Molecular Therapy is retracting this article. After investigating concerns of image duplication raised by a reader, evidence for image duplication in identical or altered fashion in Figure 7B was identified. This reuse (and in part, misrepresentation) of data without appropriate attribution represents a severe abuse of the scientific publishing system. The authors do not agree to the retraction. RETRACTED: miR-135b Delivered by Gastric Tumor Exosomes Inhibits FOXO1 Expression in Endothelial Cells and Promotes AngiogenesisBai et al.Molecular TherapyJuly 25, 2019In BriefThis article has been retracted: please see Elsevier Policy on Article Withdrawal ( http://www.elsevier.com/locate/withdrawalpolicy ). Full-Text PDF Open Archive
Cardiovascular Outcomes in Aortopathy
Authors: Kathryn W. Holmes, Sheila Markwardt, Kim A. Eagle, Richard B. Devereux, Jonathan W. Weinsaft, Federico M. Asch, Scott A. LeMaire, Cheryl L. Maslen, Howard K. Song, Dianna M. Milewicz, Siddharth K. Prakash, Dongchuan Guo, Shaine A. Morris, Reed E. Pyeritz, Rita C. Milewski, William J. Ravekes, H.C. Dietz, Ralph V. Shohet, Michael Silberbach, Mary J. Roman
Journal: Journal of the American College of Cardiology (2022)
Second Revision of the International Staging System (R2-ISS) for Overall Survival in Multiple Myeloma: A European Myeloma Network (EMN) Report Within the HARMONY Project
Authors: Mattia D'Agostino, David A. Cairns, Juan José Lahuerta, Ruth Wester, Uta Bertsch, Anders Waage, Elena Zamagni, María-Victoria Mateos, Daniele Dall'Olio, Niels W.C.J. van de Donk, Graham Jackson, Serena Rocchi, Hans Salwender, Joan Bladé Creixenti, Bronno van der Holt, Gastone Castellani, Francesca Bonello, Andrea Capra, Elias K. Mai, Jan Dürig, Francesca Gay, Sonja Zweegman, Michele Cavo, Martin F. Kaiser, Hartmut Goldschmidt, Jesús María Hernández Rivas, Alessandra Larocca, Gordon Cook, Jesús F. San-Miguel, Mario Boccadoro, Pieter Sonneveld
Journal: Journal of Clinical Oncology (2022)

PURPOSE Patients with newly diagnosed multiple myeloma (NDMM) show heterogeneous outcomes, and approximately 60% of them are at intermediate-risk according to the Revised International Staging system (R-ISS), the standard-of-care risk stratification model. Moreover, chromosome 1q gain/amplification (1q+) recently proved to be a poor prognostic factor. In this study, we revised the R-ISS by analyzing the additive value of each single risk feature, including 1q+. PATIENTS AND METHODS The European Myeloma Network, within the HARMONY project, collected individual data from 10,843 patients with NDMM enrolled in 16 clinical trials. An additive scoring system on the basis of top features predicting progression-free survival (PFS) and overall survival (OS) was developed and validated. RESULTS In the training set (N = 7,072), at a median follow-up of 75 months, ISS, del(17p), lactate dehydrogenase, t(4;14), and 1q+ had the highest impact on PFS and OS. These variables were all simultaneously present in 2,226 patients. A value was assigned to each risk feature according to their OS impact (ISS-III 1.5, ISS-II 1, del(17p) 1, high lactate dehydrogenase 1, t(4;14) 1, and 1q+ 0.5 points). Patients were stratified into four risk groups according to the total additive score: low (Second Revision of the International Staging System [R2-ISS]-I, 19.2%, 0 points), low-intermediate (II, 30.8%, 0.5-1 points), intermediate-high (III, 41.2%, 1.5-2.5 points), high (IV, 8.8%, 3-5 points). Median OS was not reached versus 109.2 versus 68.5 versus 37.9 months, and median PFS was 68 versus 45.5 versus 30.2 versus 19.9 months, respectively. The score was validated in an independent validation set (N = 3,771, of whom 1,214 were with complete data to calculate R2-ISS) maintaining its prognostic value. CONCLUSION The R2-ISS is a simple prognostic staging system allowing a better stratification of patients with intermediate-risk NDMM. The additive nature of this score fosters its future implementation with new prognostic variables.
Colonization with <i>Staphylococcus aureus</i> in healthcare workers: consequences of hand eczema
Authors: Yasemin Topal Yüksel, Sofie Marie Edslev, Anne Klose Janstrup, Mie Sonne Goldeman, Line Brok Nørreslet, Paal Skytt Andersen, Tove Agner
Journal: British Journal of Dermatology (2022)

aware of this finding as cannabinoids are an emerging therapy for chronic pruritus.This study is limited by a focus on inpatient populations, which may restrict the generalizability of our findings.It is also possible that individual patients contribute to multiple hospitalizations in our sample.Further, causal relationships cannot be inferred owing to the cross-sectional study design and lack of temporality between PN and SUDs.Nevertheless, this study is the first to detect associations between PN and opioid, cannabis and cocaine use disorders.Physicians may use these findings to guide screening for such SUDs in patients with PN and refer to healthcare specialists when appropriate.
Triple-serotype chimeric oncolytic adenovirus exerts multiple synergistic mechanisms against solid tumors
Authors: Yinghan Su, Jiang Li, Weidan Ji, Gang Wang, Lin Fang, Qin Zhang, Lin Ang, Min Zhao, Yuan Sen, Lei Chen, Junnian Zheng, Changqing Su, Lunxiu Qin
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Oncolytic virotherapy has become an important branch of cancer immunotherapy. This study investigated the efficacy of an oncolytic adenovirus (OAV), OncoViron, with synergistic mechanisms in the treatment of multiple solid tumors. Methods An OAV, OncoViron, was constructed and investigated by cytological experiments and implanted tumor models of multiple solid tumor cell lines to certify its anticancer efficacy, the synergistic effects of viral oncolysis and transgene anticancer activity of OncoViron, as well as oncolytic virotherapy combined with immunotherapy, were also verified. Results The selective replication of OncoViron mediated high expression of anticancer factors, specifically targeted a variety of solid tumors and significantly inhibited cancer cell proliferation. On a variety of implanted solid tumor models in immunodeficient mice, immunocompetent mice, and humanized mice, OncoViron showed great anticancer effects on its own and in combination with programmed death 1 (PD-1) antibody and chimeric antigen receptor (CAR) T cells. Pathological examination, single-cell sequencing, and spatial transcriptome analysis of animal implanted tumor specimens confirmed that OncoViron significantly altered the gene expression profile of infected cancer cells, not only recruiting a large number of lymphocytes, natural killer cells, and mononuclear macrophages into tumor microenvironment (TME) and activated immune cells, especially T cells but also inducing M1 polarization of macrophages and promoting the release of more immune cytokines, thereby remodeling the TME for coordinating PD-1 antibody or CAR T therapy. Conclusions The chimeric OncoViron is a novel broad-spectrum anticancer product with multiple mechanisms of synergistic and potentiated immunotherapy, creating a good opportunity for combined immunotherapy against solid tumors.
Radiation segmentectomy for curative intent of unresectable very early to early stage hepatocellular carcinoma (RASER): a single-centre, single-arm study
Authors: Edward Kim, Alex Sher, Ghadi Abboud, Myron Schwartz, Marcelo Facciuto, Parissa Tabrizian, Karin Knešaurek, Aaron Fischman, Rahul Patel, Scott Nowakowski, Josep Llovet, Bachir Taouli, Robert Lookstein
Journal: The Lancet. Gastroenterology & hepatology (2022)